cAMP/Protein Kinase A Signaling Inhibits Dlx5 Expression via Activation of CREB and Subsequent C/EBPβ Induction in 3T3-L1 Preadipocytes

Lee, Hye-Lim; Qadir, Abdul; Park, Hyun-Jung; Chung, Eun-Kyung; Lee, Yun‐Sil; Woo, Kyung Mi; Ryoo, Hyun‐Mo; Kim, Hyun Jeong; Baek, Jeong‐Hwa

doi:10.3390/ijms19103161

Cited by 18 publications

(14 citation statements)

References 26 publications

(42 reference statements)

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“…Although the mechanism is unknown, adipogenesis requires the availability of intracellular cAMP for the differentiation of 3T3L1 preadipocytes into adipocytes that is concomitant with the programmed expression of the genes that comprise an adipocyte-specific profile which is stimulated by phosphodiesterase inhibitors including IBMX (Spiegelman et al 1993). More recently, we have seen that IBMX permits CREB phosphorylation through the PKA signaling pathway and upregulates C/EBPβ to stimulate adipogenesis in 3T3-L1 preadipocytes (Zhang et al 2004, Lee et al 2018.…”

Section: Adipogenesismentioning

confidence: 99%

PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies

London

Bloyd

Stratakis

2020

Journal of Endocrinology

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Both direct and indirect evidence demonstrate a central role for the cAMP-dependent protein kinase (PKA) signaling pathway in the regulation of energy balance and metabolism across multiple systems. However, the ubiquitous pattern of PKA expression across cell types poses a challenge in pinpointing its tissue-specific regulatory functions and further characterizing its many downstream effects in certain organs or cells. Mouse models of PKA deficiency and over-expression and studies in living cells have helped clarify PKA function in adipose tissue (AT), liver, adrenal, pancreas, and specific brain nuclei, as they pertain to energy balance and metabolic dysregulation. Limited studies in humans suggest differential regulation of PKA in AT of obese compared to lean individuals and an overall dysregulation of PKA signaling in obesity. Despite its complexity, under normal physiologic conditions, the PKA system is tightly regulated by changes in cAMP concentrations upstream via adenylate cyclase and downstream by phosphodiesterase-mediated cAMP degradation to AMP and by changes in PKA holoenzyme stability. Adjustments in the PKA system appear to be important to the development and maintenance of the obese state and its associated metabolic perturbations. In this review we discuss the important role of PKA in obesity and its involvement in resistance to obesity, through studies in humans and in mouse models, with a focus on the regulation of PKA in energy expenditure, intake behavior, and lipid and glucose metabolism.

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Section: Adipogenesismentioning

confidence: 99%

PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies

London

Bloyd

Stratakis

2020

Journal of Endocrinology

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“…IBMX increases the intracellular cAMP concentration by inhibiting cAMP phosphodiesterase. The increase in cAMP levels activates protein kinase A (PKA) and activated PKA improves the activity and expression of cAMP-related binding protein (CREB) [39]. CREB binds to the MITF promoter, leading to upregulation of MITF gene expression.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Anti-Melanogenic Activities of Heat-Treated Licorice (Wongam, Glycyrrhiza glabra × G. uralensis) Extract

Kang

Jang

et al. 2021

CIMB

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Melanin is a brown or black pigment that protects skin from ultraviolet radiation and reactive oxygen species (ROS). However, overproduction of melanin is associated with lentigines, melasma, freckles and skin cancer. Licorice has shown antioxidant, anti-tumor, anti-platelet, anti-inflammatory and immunomodulatory activities and is used as a natural treatment for skin whitening. We aimed to confirm the potential of Wongam, a new cultivar of licorice developed by the Rural Development Administration (RDA), as a whitening agent in cosmetics. In addition, we verified the effect of heat treatment on the bioactivity of licorice by comparing antioxidant and anti-melanogenic activities of licorice extract before and after heating (130 °C). The heat-treated licorice extract (WH-130) showed higher radical-scavenging activities in the ABTS+ (2,2′-azino-bis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays. In addition, WH-130 inhibited melanogenesis more effectively due to downregulation of tyrosinase in B16F10 melanoma cells than non-heated licorice extract. Moreover, heat treatment increased total phenolic content. In particular, isoliquiritigenin, an antioxidant and anti-melanogenic compound of licorice, was produced by heat treatment. In conclusion, WH-130, with increased levels of bioactive phenolics such as isoliquiritigenin, has potential for development into a novel skin whitening material with applications in cosmetics.

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“…It is well elucidated that cAMP/PKA signal pathway plays important roles in adipogenesis and thermogenesis of brown adipocytes [14,40]. Especially for brown adipocytes, activation of β-AR triggers a kinase cascade from PKA to p38 MAPK in mouse adipocytes to increase the expression of UCP-1 (41)(42).…”

Section: Discussionmentioning

confidence: 99%

C-type Natriuretic Peptide Promotes Adipogenic Differentiation of Goat Adipose Derived Stem Cells via cGMP/PKG/ p38 MAPK Signal Pathway

Fan

Yan

Miao

et al. 2020

Preprint

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BackgroundTwo types of adipose tissue, white adipose and brown adipose, have been identified in mammals. For goat, adipose tissue also plays an important role in improving meat and milk quality. C-type natriuretic peptide (CNP) is a member of natriuretic peptide family. Once CNP binds to natriuretic peptide receptor B (NPR-B), NPR-B induces the production of cGMP, thereby activating PKG and downstream targets. The expression of CNP and NPR-B in adipose tissue led to a hypothesis that CNP could have roles involving in regulation of adipogenesis in goat. However, there are few studies on the relationship between CNP and adipogenesis in goat. In the present study, goat adipose derived stem cells (ADSCs) were isolated and employed to investigate the effect of CNP on adipogenesis in goat.ResultsDuring adipogenic differentiation in goat ADSCs, the expression of NPR-B increased at 4 d and 8 d and reduced at 12 d after differentiation. When goat ADSCs were treated with 100 nM and 1000 nM CNP during adipogenic differentiation, there are more accumulation of lipid droplets in the cytoplasm and the up-regulation in the expression of adipogenesis relative genes including PPAR-γ, FASN and LPL. Interestingly, the expression level of brown adipose genes UCP-1 and PGC-1α were also up-regulated. Furthermore, the cGMP level was increased after treatment with CNP. Adding cGMP analogues 8-pCPT-cGMP (PKG activator) could increase adipogenesis efficiency, and adding both PKG inhibitor Rp-8-CPT-cGMP and CNP inhibited adipogenic differentiation. After treatment with CNP or PKG activator, the phosphorylation of p38 MAPK, MK2 and ATF2 were up-regulated, and their phosphorylation were significantly inhibited when CNP and PKG inhibitor were added simultaneously. SB203580 is the specific inhibitor for p38 MAPK. After treatment with CNP and SB203580 simultaneously, the adipogenic differentiation efficiency of goat ADSCs was significantly inhibited, and the expression of UCP-1 and PGC-1α were also reduced. ConclusionsCNP could promote adipogenic differentiation of goat ADSCs. The stimulative effect of CNP on adipose differentiation depends on the cGMP/PKG/ p38 MAPK signal pathway. Our study will be helpful to understand the regulation mechanism of goat adipose differentiation, especially brown adipose differentiation.

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cAMP/Protein Kinase A Signaling Inhibits Dlx5 Expression via Activation of CREB and Subsequent C/EBPβ Induction in 3T3-L1 Preadipocytes

Cited by 18 publications

References 26 publications

PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies

PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies

Antioxidant and Anti-Melanogenic Activities of Heat-Treated Licorice (Wongam, Glycyrrhiza glabra × G. uralensis) Extract

C-type Natriuretic Peptide Promotes Adipogenic Differentiation of Goat Adipose Derived Stem Cells via cGMP/PKG/ p38 MAPK Signal Pathway

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